2014 Research Grant Awards

The following departmental faculty were awarded competitive and non-competitive research grants during calendar year 2014.

Dr. Richard Moon, Medical Director of the Center for Hyperbaric Medicine and Environmental Physiology, received a two-year $199,949 Subaward from Creare Inc., for an application entitled “Advanced Technologies for Reducing Decompression Obligation in Extreme Dives”.

The objective of this research project is to develop advanced technologies for management decompression sickness (DCS) during extreme military dives. Decompression sickness (DCS) is a physical manifestation of decompression stress (DS), defined as the physiologic response to dissolved gas coming out of solution into the venous circulation as a body moves from a high pressure to low pressure environment, such as surfacing from a dive. At present, the only measure of DS is the direct manifestation of symptoms (DCS). Duke will serve as the primary animal testing facility for the Phase II project using the swine model.

The VA division would like to congratulate DIG recipient Thomas Van de Ven, MD, PhD, who has received a 3-year, $1.5 million Department of Defense (DoD) Neurosensory Research grant renewal for his VIPER (Veterans Integrated Pain Evaluation Research) study entitled “Chronic Pain after Amputation: Inflammatory Mechanisms, Novel Analgesic Pathways, and Improved Patient Safety.”

Dr. Van de Ven and his staff will be funded for 3 years from this grant, and it will allow him to continue his work in chronic pain in amputation patients, specifically inflammatory mechanisms, novel analgesic pathways, and improved patient safety. Other personnel involved in this study are LTC Dr. Chester Buckenmaier, Associate Professor at Uniformed Services University of the Health Sciences, and Dr. Andrew Shaw, former Duke faculty and now Division Chief of Cardiothoracic Anesthesiology at Vanderbilt University Medical Center.

The VA division is delighted to share his success with our scientific community and look forward to his work assisting and honoring our wounded warriors.

Miles Berger, MD, PhD, Medical Instructor in the Otolaryngology, Head, Neck, and Neuroanesthesiology Division was awarded a two-year $150,000 International Anesthesia Research Society Mentored Research Award entitled “The trajectory and significance of perioperative changes in AD biomarkers”.

Multiple independent laboratories have used cell culture studies, biochemical assays and animal models to show that surgical exposure and anesthetic drugs can accelerate Alzheimer’s Disease pathology. In particular, surgical exposure and/or anesthetic drugs have been shown to increase the levels of amyloid beta and tau, two key proteins thought to play key roles in causing Alzheimer’s Disease. Furthermore, surgery and anesthesia have been associated with post-operative delirium and cognitive impairments in some of our patients. It is less clear, however, whether surgery and/or anesthesia actually promote Alzheimer’s disease pathology in our patients, and whether such effects might explain part of the post-operative delirium and/or cognitive impairments seen in some patients. Our preliminary results show that cerebrospinal fluid (CSF) tau levels increase significantly within the first day after surgery and anesthesia in a subset of patients. In this research study, we propose to assess the long term trajectory of these CSF tau increases, and to determine whether these tau increases are associated with post- operative delirium and/or cognitive trajectory. Furthermore, we will use in vivo neuroimaging to determine whether perioperative CSF tau increases are associated with altered functional brain connectivity after anesthesia and surgery. These studies will help provide a translational framework to determine how anesthesia and surgery affect Alzheimer’s Disease pathology in the human brain, and/or whether such affects correlate with post-operative delirium and cognitive trajectory.

Wei Yang, PhD, Assistant Professor in the Division of Basic Sciences, was awarded $7,000 from the Duke University School of Medicine Core Facility Voucher Program for an application entitled “Genome-wide analysis of chromatin modification by SUMO in mouse brain”. Dr. Yang has generated several unique SUMO transgenic and knockout mice models, including SUMO knockout mice, neuron-specific SUMO knockdown mice, and Cre-inducible SUMO transgenic mice. Using these mice models, he found that a functional SUMO conjugation pathway is essential for emotionality and cognition, and he also characterized the SUMO-modified proteome in the post-ischemic brains. The voucher will be used to identify the genomic loci occupied by SUMOylated proteins using chromatin immunoprecipitation coupled to next generation sequencing (ChIP-Seq). This pilot project is expected to establish a platform for future studies to uncover the mechanisms linking SUMO conjugation to neuronal functions in vivo.

An inter-professional team in the Human Simulation and Patient Safety Center (HSPSC) received a 1-year, $25,000 research award from the Social Entrepreneurship Accelerator at Duke (SEAD) for a project entitled “Postpartum Hemorrhage Education Via Simulation”.

The team is pioneering the use of scalable, distributable healthcare simulation using commercial game technology with a multi-player module that specifically addresses postpartum hemorrhage (PPH). As a proof-of-concept for global health, the PPH simulation software will be used to address gaps in care at Mulago International Referral Hospital in Kampala, Uganda, and to decrease disparities in healthcare education. We will host inter-professional, interactive, games-based simulation training sessions from Durham to Mulago using the Internet. This pilot program aims to reduce the incidence of postpartum hemorrhage, and to serve as a broader model for using simulation to scale education and to spread virtual learning through the developing world in resource-poor settings. Additionally, we hope to use preliminary data to support a future proposal to study the efficacy of screen-based/games-based learning in global health. Key personnel include: Jeff Taekman (MD) who is the Principal Investigator, Megan Foureman (CRNA, MSN), Amy Mauritz (MD), Adeyemi Olufolabi (MB.BS; DCH; FRCA), Michael Steele (BS) and Genevieve DeMaria (BS).

Ru-Rong Ji, PhD, of the Sensory Plasticity and Pain Research Group in Division of Basic Sciences, received a new 5-year $1,739,065 NIH Research Grant (R01) from the National Institute of Neurological Disorders and Stroke (NIHDS) for his research project entitled “Resolution Pathway of Pain”. More than 30 million Americans suffer from unrelieved chronic pain, which is regarded as a disease with its own pathology. Current studies focus on how pain is induced, but it is unclear how acute pain naturally resolves. We hypothesize that disruption of local active pro-resolving processing will result in chronic pain. Our recent studies have shown that the pro-resolution lipid mediators (PRLMs) such as resolvins and protectins, derived from omega-3 unsaturated fatty acids DHA and EPA, are potent inhibitors of inflammatory and neuropathic pain. Mechanistically, PRLMs not only normalize synaptic plasticity but also suppress glial activation in the spinal cord. Resolvins are also potent endogenous inhibitors of TRPA1 or TRPV1 (IC50=1-10 nM). However, the signaling mechanisms of PRLMs are elusive. β-arrestin-2 (βarr2) is a scaffold protein that is classically involved in desensitization of GPCRs. However, the unique role of βarr2 in regulating NMDA receptor function and inflammatory/neuropathic pain is unknown. The overall goal of this application is to investigate how βarr2 arrests pain and whether PRLMs resolve pain via βarr2. Our approach is multidisciplinary that combines genetic manipulation (transgenic mice, conditional knockout mice, gene therapy), electrophysiology, and behavioral testing for evoked pain and spontaneous pain (CPP). The proposed study will not only identify a pro-resolution pathway for “pain arrest” but may also lead to the development of novel pain therapeutics.